The major goal of this project is to elucidate the mechanisms by which excessive exposure to noise (or other noxious agents) causes cellular degeneration in the inner ear. Another goal is to determine how the magnitude and pattern of hearing loss and structural damage are altered as the physical parameters of the stimulus (e.g. frequency, intensity, duration and scheduling of noise) are systematically varied. These studies are designed to identify the general principles of injury in the inner ear rather than to specify damage-risk criteria for human exposures. In addition to the experiments involving noise exposure, studies are planned in the areas of morphometric analysis of cochlear structures, cochlear perfusion and ischemia. Work in these additional areas is essential in order to attain our long-term goals. More objective methods for evaluating cellular alterations are needed in order to detect early or mild cochlear damage. To this end, morphometric analysis of various cellular and subcellular parameters in normal cochleas will provide a baseline to which data from damaged ears can be compared. The studies involving cochlear perfusions and ischemia will permit the testing of some of the current hypotheses concerning mechanisms of damage in the inner ear. Some of the experimental animals will be trained by food-reward, operant-conditioning techniques so that measures of auditory function (e.g. pure-tone thresholds, temporal integration functions, frequency DL's) can be obtained before, during and after their exposure to noise. Histological evaluation of the specimens will include detailed phase-contrast study of plastic-embedded flat preparations. Counts of missing sensory and supporting cells will be made and cytocochleograms prepared for all specimens. Multiple areas in the normal and pathological cochleas will then be sectioned for light and/or transmission electron microscopic study in order to conduct the morphometric analyses.